| Objective:To investigate the therapeutic effect of Cangxitongbi capsule on knee osteoarthritis in rats and its mechanism based on NLRP3/Caspase-1 signaling pathway.In order to provide a theoretical basis for the prevention and treatment of knee osteoarthritis with Cangxitongbi capsule,and provide new ideas for the clinical drug research of knee osteoarthritis.Methods:Thirty 4-week-old healthy male rats were randomly divided into 5 groups:blank control group(control group),model group(model group),low-dose Cangxitongbi capsule group(L group),medium dose Cangxitongbi capsule group(M group),and high-dose Cangxitongbi capsule group(H group),with 6 rats in each group.After successful modeling,the blank control group and model group were given 3ml of physiological saline by gavage,while the low,medium,and high dose Cang Xi Tong Bi capsule administration groups were given 3ml of Cang Xi Tong Bi capsule solution of different concentrations(17.5mg/ml,35 mg/ml,70 mg/ml)by gavage,once a day.After gastric lavage for four weeks,the rats were euthanized and various indicators such as abdominal aortic blood and knee joint cartilage tissue were obtained for testing.Finally,the state of the rat knee joint cartilage was observed using direct vision and HE staining methods;Elisa detects IL-18 and IL-1 in different groups of rats β Content of;Western Blot and detection of the expression levels of NLRP3,Casepase-1,MMP-1,MMP-13 proteins and related genes in knee cartilage of different groups of rats.Results:1.Compared with the control group,the cartilage thickness of the model group was significantly thinner,the surface was rough,the cartilage surface appeared depression and cartilage debris,and the articular surface was dull under direct vision.In groups L,M,and H,the thickness of cartilage was thinner,the surface was rough,and the color was cloudy.However,compared with the model group,the degree of knee joint damage in L,M and H groups was H group<M group<L group<model group.(2)The results of HE staining showed that in the control group,HE staining was mainly matrix,the staining was uniform,and the chondrocytes were distributed regularly.In the model group,the continuity of the superficial cartilage was interrupted,the matrix staining was uneven,and the chondrocytes were significantly reduced.The results of HE staining in L,M and H groups were significantly improved,and the degree of improvement was positively correlated with the drug concentration.(3)The expression levels of inflammatory factors IL-18 and IL-1β in the control group were the lowest,and those in the model group were the highest(P<0.05).Different concentrations of Cangxi Tongbi capsule could effectively reduce the expression of inflammatory factors in peripheral blood(P<0.05).The expression levels of inflammatory factors in L group were higher than M group and H group,and the difference was statistically significant(P<0.05).(4)Compared with the control group,the expression levels of NLRR3,Caspase-1,MMP-1 and MMP-13 proteins in the knee cartilage of the model group were significantly increased(P<0.05).Different concentrations of Cangxi Tongbi capsules could effectively reduce the expression levels of NLRR3,Caspase-1,MMP-1,and MMP-13 proteins in knee cartilage of KOA model rats(P<0.05).The expression level of the above proteins in group H was the lowest,followed by group M,and the expression level of the above proteins in group L was the highest.The difference was statistically significant(P<0.05).(5)Compared with the control group,the expression levels of NLRR3 mRNA,Caspase-1 mRNA,MMP-1 mRNA and MMP-13 mRNA in the knee cartilage of the model group were significantly increased(P<0.05).Compared with the model group,the expression levels of NLRR3 mRNA,Caspase-1 mRNA,MMP-1 mRNA and MMP-13 mRNA in the L,H and M groups were decreased(P<0.05),and the degree of reduction was inversely proportional to the concentration of Cangxi Tongbi capsule.The difference was statistically significant(P<0.05).Conclusion:1.NLRP3/Caspase-1 signaling pathway is an important signaling pathway in the development of KOA,and it is also another effective target for the study of the mechanism of action of drugs for KOA.2.Cangxitongbi capsule can effectively inhibit NLRP3/Caspase-1 signaling pathway,thereby inhibiting inflammatory response in KOA model rats and accelerating the repair of degenerative cartilage,so as to achieve the goal of treating knee osteoarthritis.3.Different concentrations of Cangxitongbi capsule have different therapeutic effects on KOA model rats,and the therapeutic effect of high concentration group is better than that of middle dose group and low dose group. |
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